Topics in Current Chemistry (2020) 378:8
1 3
Additionally, the capping ligand confers a given surface charge on NPs, which
greatly affects the resulting skin penetration rate. For instance, positively charged
drug carriers, such as dendrimers and liposomes, are well-known to induce greater
drug delivery in the skin [57, 58]. In this context, Fernandes et al. [50] showed that
positive charged PEG-capped AuNPs were found in the skin at levels from 2- to
6-fold higher than in their negative counterparts. These results were obtained both
for spherical- and for rod-shaped NPs, and were in agreement with the enhanced
skin permeation of cationic liposomes, which was attributed to the “Donnan exclusion effect” and to the better interaction of cationic particles with negatively charged
skin cells [59]. Furthermore, in this study, they also showed that AuNPs functionalized with cell penetrating peptides (CPPs) TAT and R7 were found in the skin in
larger quantities than PEGylated AuNPs, demonstrating that bioconjugation greatly
enhances skin penetration rate [50].
In an alternative strategy, Lee and co-workers investigated the influence of the
surface charge of Au-nanorods on skin penetration using a layer‐by‐layer (LbL)
polyelectrolyte coating technique [60]. They observed that negative charged CTAB/
PSS-capped Au-nanorods penetrated more rapidly through the skin than the positive ones (CTAB- and CTAB/PSS/PDADMAC-capped). For this, three different
multi-layer coated Au-nanorods with a particle size of 18 × 40 nm were used: two
positively charged, CTAB- and CTAB/PSS/PDADMAC-capped, and one negatively charged, CTAB/PSS-capped. These surprising results were attributed to both
aggregation of the positively charged Au-nanorods on the stratum corneum and the
adsorption of proteins released from the dermis layer to the surface of Au-nanorods.
In line with these results, Mahmoud et al. [61] observed that positively charged Aunanorods aggregated extensively upon exposure to human skin compared to their
negatively and neutrally charged counterparts. They attributed these findings to the
adsorption of proteins released from the dermis layer to the surface of Au-nanorods.
In this latter study, they prepared 49.5 × 12.0 nm Au-nanorods capped with four different surface ligands: cetyltrimethylammonium (CTAB), polyacrylic acid (PAA),
poly(allylamine hydrochloride) (PAH), and methoxy-polyethylene glycol-thiol
(m-PEG-SH). Conversely, Hao et al. [62] also investigated the influence of the surface charge on the skin penetration of spherical AuNPs using human reconstructed
3D Episkin model. In this study, three different surfaces charged 5 nm-AuNPs
capped with citrate (negative), PVP (neutral), and CTAB (positive) were tested.
They observed that, although all AuNPs induced the phase change of lipid lamella
and passed through the epidermis, positively charged AuNPs exhibited the most efficient skin penetration through both the paracellular routes and the transcellular pathway when compared to neutrally or negatively charged NPs.
An interesting alternative for stabilizing NP surfaces is PEGylation, which is
an approach commonly used for improving the drug and gene delivery efficiency
of NP-based systems to target cells and tissues [63]. Hsiao and co-workers [64]
employed this approach to investigate the positive effects of polyethylene glycol
(HS-PEG-COOH) and HS-PEG-oleylamine (OAm) functionalization on the skin
permeation of spherical 10 nm AuNPs. Using an in vivo rat model, they showed that
PEG- and PEG-OAm-functionalized AuNPs were able to overcome the skin barrier and deposit in the deeper subcutaneous adipose tissue. Moreover, the follicular
226
Reprinted from the journal
1 3
Additionally, the capping ligand confers a given surface charge on NPs, which
greatly affects the resulting skin penetration rate. For instance, positively charged
drug carriers, such as dendrimers and liposomes, are well-known to induce greater
drug delivery in the skin [57, 58]. In this context, Fernandes et al. [50] showed that
positive charged PEG-capped AuNPs were found in the skin at levels from 2- to
6-fold higher than in their negative counterparts. These results were obtained both
for spherical- and for rod-shaped NPs, and were in agreement with the enhanced
skin permeation of cationic liposomes, which was attributed to the “Donnan exclusion effect” and to the better interaction of cationic particles with negatively charged
skin cells [59]. Furthermore, in this study, they also showed that AuNPs functionalized with cell penetrating peptides (CPPs) TAT and R7 were found in the skin in
larger quantities than PEGylated AuNPs, demonstrating that bioconjugation greatly
enhances skin penetration rate [50].
In an alternative strategy, Lee and co-workers investigated the influence of the
surface charge of Au-nanorods on skin penetration using a layer‐by‐layer (LbL)
polyelectrolyte coating technique [60]. They observed that negative charged CTAB/
PSS-capped Au-nanorods penetrated more rapidly through the skin than the positive ones (CTAB- and CTAB/PSS/PDADMAC-capped). For this, three different
multi-layer coated Au-nanorods with a particle size of 18 × 40 nm were used: two
positively charged, CTAB- and CTAB/PSS/PDADMAC-capped, and one negatively charged, CTAB/PSS-capped. These surprising results were attributed to both
aggregation of the positively charged Au-nanorods on the stratum corneum and the
adsorption of proteins released from the dermis layer to the surface of Au-nanorods.
In line with these results, Mahmoud et al. [61] observed that positively charged Aunanorods aggregated extensively upon exposure to human skin compared to their
negatively and neutrally charged counterparts. They attributed these findings to the
adsorption of proteins released from the dermis layer to the surface of Au-nanorods.
In this latter study, they prepared 49.5 × 12.0 nm Au-nanorods capped with four different surface ligands: cetyltrimethylammonium (CTAB), polyacrylic acid (PAA),
poly(allylamine hydrochloride) (PAH), and methoxy-polyethylene glycol-thiol
(m-PEG-SH). Conversely, Hao et al. [62] also investigated the influence of the surface charge on the skin penetration of spherical AuNPs using human reconstructed
3D Episkin model. In this study, three different surfaces charged 5 nm-AuNPs
capped with citrate (negative), PVP (neutral), and CTAB (positive) were tested.
They observed that, although all AuNPs induced the phase change of lipid lamella
and passed through the epidermis, positively charged AuNPs exhibited the most efficient skin penetration through both the paracellular routes and the transcellular pathway when compared to neutrally or negatively charged NPs.
An interesting alternative for stabilizing NP surfaces is PEGylation, which is
an approach commonly used for improving the drug and gene delivery efficiency
of NP-based systems to target cells and tissues [63]. Hsiao and co-workers [64]
employed this approach to investigate the positive effects of polyethylene glycol
(HS-PEG-COOH) and HS-PEG-oleylamine (OAm) functionalization on the skin
permeation of spherical 10 nm AuNPs. Using an in vivo rat model, they showed that
PEG- and PEG-OAm-functionalized AuNPs were able to overcome the skin barrier and deposit in the deeper subcutaneous adipose tissue. Moreover, the follicular
226
Reprinted from the journal